(+)-Hydrocodone is an opioid with utility as a pharmaceutical compound because of its analgesic properties. Furthermore, (+)-hydrocodone is a key intermediate in the synthesis of other opioids, and in particular unnatural (+)-opioids such as (+)-morphine that have known pharmacological effects (e.g., low micro-molar affinity for the site of the N-methyl-D-aspartate (NMDA) receptor in the rat forebrain, and suggested clinical potential in the treatment of neuropathic pain). (See, e.g., Neuroscience Letters 295 (2000), 21-24.) (+)-Hydrocodone may have significant therapeutic potential if used alone, or if used in combination with other drugs to treat pain, inflammation, cancer, immune disorders, and other diseases.
(+)-Hydrocodone, as illustrated by the structure below, has a fused, tetracyclic core ring structure that includes a furan ring.

It can be prepared by processes that include subjecting dihydrosinomenine or dihydrosinomeninone, both of which as illustrated below include a fused, tricyclic core ring structure, to a furan ring closure or ring formation reaction.

However, current methods of converting dihydrosinomenine to (+)-hydrocodone typically involve the use of large excesses of polyphosphoric acid or a mixture of methanesulfonic acid and phosphorus pentoxide, while current methods of converting dihydrosinomeninone to (+)-hydrocodone typically involve the use of harsh reaction conditions (e.g., boiling dihydrosinomeninone in 50% sulfuric acid). (See, e.g., Goto, K. et al., Acta Phytochim. (Japan), 1949, 15, 187-191; Lijuma, I. et al., C. J. Org. Chem., 1978, 43(7), 1462-1463; and/or, Whittall, J. et al., UK Patent Application No. GB2392670A.)
The currently employed processes for synthesizing (+)-hydrocodone are undesirable for a number of reasons. For example, one or more of these processes may suffer from inefficiency because of the need for a large amount of base to quench the excessive amount of acid used in the reaction, and/or because of the large amount of energy needed to boil the reaction mixture. Such processes may therefore be difficult and expensive to scale up.
In view of the foregoing, a need continues to exist for an improved process for preparing (+)-hydrocodone, as well as other compounds structurally related thereto.